In sub-Saharan African countries there is debate regarding the feasibility of initiating large-scale highly active antiretroviral therapy (HAART) through the public sector, because of financial and health infrastructure constraints. At times, this debate may be poorly informed due to a lack of evidence regarding the costs and cost-effectiveness of HAART in these countries. We propose to evaluate the costs and cost-effectiveness of HAART in Botswana, a lower-middle income country with very high HIV prevalence. With the impending implementation of a large-scale HAART program, the Government of Botswana faces important decisions regarding the best use of available resources in scaling up HAART to a national level. This study aims to inform these policy decisions, and impact international approaches to the delivery of HAART in Botswana and other countries in the region. In addition to evaluating costs, the study will use mathematical modeling techniques to estimate the effectiveness of HAART in reducing HIV-related morbidity and mortality in Botswana. Specific aims are to estimate: (1) the incremental cost-effectiveness of HAART compared to the current standard of care without HAART. (2) The average costs per person associated with HAART, to estimate the long-term resources required for sustaining a national program. This will include variations in costs in urban and more rural sites; variations due to the initiation of HAART in advanced, mid or early stage disease; and the changes in demands on health services over time in specific sites in Botswana with the introduction of HAART. (3) The incremental cost-effectiveness of commencing HAART at advanced, mid or early stage HIV disease, to evaluate eligibility criteria for the national HAART program. (4) The incremental cost-effectiveness of different models of HAART delivery, to elucidate the models of care delivery that are most cost-effective in Botswana health care settings. (5) The incremental cost-effectiveness of different drug regimens, to help elucidate the drug regimens that are most cost-effective in Botswana health care settings. [unreadable] [unreadable]